Non-infectious Uveitis MedDRA version: 22.1 Level: LLT Classification code 10022557 Term: Intermediate uveitis System Organ Class: 100000004853 MedDRA version: 20.1 Level: LLT Classification code 10036370 Term: Posterior uveitis System Organ Class: 100000004862 MedDRA version: 20.0 Level: LLT Classification code 10033687 Term: Panuveitis System Organ Class: 100000004853
Conditions
Sponsors
Gilead Sciences, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Judged to be in good health as determined by the investigator based on the results of medical history, laboratory screening profile, physical examination, chest x-ray, and 12-lead electrocardiogram performed during Screening - A negative serum pregnancy test is required for female subjects of childbearing potential - Male subjects and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception - Lactating females must agree to discontinue nursing before the study drug is administered - Male or female subjects who are = 18 years of age on the day of signing informed consent - Diagnosed with non-infectious intermediate-, posterior-, or pan-uveitis - Active uveitic disease at the Day 1/Baseline visit as defined by the presence of at least 1 of the following parameters in at least one eye despite at least 2 weeks of maintenance therapy with oral prednisone (= 10 mg/day to = 60 mg/day) or an oral corticosteroid equivalent - On oral prednisone = 10 mg/day to = 60 mg/day (or oral corticosteroid equivalent) for 2 or more weeks immediately prior to and including Day 1/Baseline - Documented prior adequate response to oral corticosteroids (equivalent of oral prednisone up to 1 mg/kg/day) - No evidence of active tuberculosis (TB), previously treated for TB or newly identified latent TB during screening - Able and willing to sign the informed consent as approved by the Independent Ethics Committee (IEC)/Institutional Review Board (IRB). Written consent must be provided before initiating any screening evaluations. Subjects must have read and understood the ICF, must fully understand the requirements of the study, and must be willing to comply with all study visits and assessments. Subjects who cannot understand the ICF may not be enrolled by a guardian or any other individual. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 223 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 25
Exclusion criteria
Exclusion criteria: - The presence of isolated anterior uveitis - The presence of macular edema as the only sign of intermediate-, posterior- or pan-uveitis - Intolerance to or prior inadequate response to high-dose oral corticosteroids (equivalent of oral prednisone 1 mg/kg/day or 60 to 80 mg/day) - Confirmed or suspected infectious uveitis - Presumed ocular histoplasmosis syndrome (as determined by the investigator) - Ocular masquerade syndromes such as ocular lymphoma (as determined by the investigator) - Serpiginous choroidopathy - Corneal or lens opacity that precludes visualization of the fundus or that likely requires cataract surgery during the duration of the trial - Subject with elevated intraocular pressure and/or Severe glaucoma who is unable to meet one or more of the protocol defined criteria within the screening period - Exposure to a systemic carbonic anhydrase inhibitor within 1 week prior to Screening - Best Corrected Visual Acuity (BCVA) less than 20 letters (Early Treatment Diabetic Retinopathy Study) in any eye at the Day 1/Baseline Visit - Previous exposure to an approved or experimental JAK inhibitor therapy - Any condition preventing the evaluation/assessment of both eyes for eligibility criteria and/or for the presence of treatment failure criteria, as detailed in the protocol - Exposure to anti-tumor necrosis factor (TNF) therapy or any biologic therapy within 4 weeks of Day 1/Baseline (as per the protocol). - Received intravitreal anti-VEGF therapy within 45 days of the Day 1/Baseline visit [i.e Lucentis® (ranibizumab) or Avastin® (bevacizumab)] or within 60 days of the Day 1/Baseline visit for anti-VEGF Trap (i.e, aflibercept) - Use of more than 1 accepted immunosuppressive therapy (not counting corticosteroids) at Day 1/Baseline - Using concomitant immunosuppressive therapy at Day 1/Baseline other than methotrexate or azathioprine - If entering the study on 1 concomitant immunosuppressive therapy, dose has been increased within 28 days prior to Day 1/Baseline visit or is not within the allowable doses defined in the protocol - Systemic inflammatory disease requiring continued therapy with oral corticosteroids or a prohibited immunosuppressive agent at screening or Day 1/Baseline - Received Retisert® (glucocorticosteroid implant) within 3 years prior to the Day 1/Baseline visit or has had complications related to the device - Received intraocular or periocular corticosteroids within 30 days prior to Day 1/Baseline visit - Presence of proliferative or severe non-proliferative diabetic retinopathy or clinically significant macular edema due to diabetic retinopathy - Presence of neovascular/wet age-related macular degeneration - Presence of a clinically significant abnormality of vitreo-retinal interface per investigator discretion (i.e., vitreomacular traction, epiretinal membranes, etc.) with the potential for macular structural damage independent of the inflammatory process - Presence of severe vitreous haze that precludes visualization of the fundus at the Day 1/Baseline visit - Received Ozurdex® (dexamethasone implant) within 3 months prior to the Day 1/Baseline visit - Received intravitreal methotrexate within 90 days prior to the Day 1/Baseline visit - Use of cyclophosphamide within 30 days prior to the Day 1/Baseline visit - Evidence of any clinically significant (as per the judgement of the investigator) active or chronic recurring infection, opportunistic infection, or immunodeficiency syndrome - Severe (anaphylactic
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: - Evaluate the efficacy of filgotinib versus placebo as measured by the time to treatment failure - Evaluate the efficacy of filgotinib versus placebo as measured by the change in VH grade in each eye (NEI/SUN criteria) - Evaluate the efficacy of filgotinib versus placebo as measured by the change in AC cell grade in each eye - Evaluate the efficacy of filgotinib versus placebo as measured by the change in logMAR BCVA in each eye - Evaluate the efficacy of filgotinib versus placebo as measured by the change in central retinal thickness in each eye - Evaluate the efficacy of filgotinib versus placebo as measured by the time to development of macular edema in at least one eye as determined by OCT - Evaluate the safety and tolerability of filgotinib - Evaluate the pharmacokinetics of filgotinib and its metabolite GS-829845;Main Objective: To evaluate the efficacy of filgotinib versus placebo for the treatment of the signs and symptoms of non-infectious uveitis as measured by the proportion of subjects failing treatment for active non-infectious uveitis by Week 24;Primary end point(s): Proportion of subjects failing treatment for active non-infectious uveitis;Timepoint(s) of evaluation of this end point: By week 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary endpoints of this study are: 1. Time to treatment failure 2. Change in VH grade in each eye (NEI/SUN criteria) 3. Change in AC cell grade in each eye 4. Change in logMAR BCVA in each eye 5. Log change in central retinal thickness in each eye 6. Time to development of macular edema in at least one eye as determined by OCT 7. Pharmacokinetic characteristics for filgotinib and its metabolite GS-829845;Timepoint(s) of evaluation of this end point: 1. On or after Week 6 2. Up to Week 52/End of Treatment visit or Early Termination visit 3. Up to Week 52/End of Treatment visit or Early Termination visit 4. Up to Week 52/End of Treatment visit or Early Termination visit 5. Up to Week 52/End of Treatment visit or Early Termination visit 6. On or after Week 6 7. From baseline to Week 52/End of Treatment visit or Early Termination visit | — |
Countries
Australia, Canada, Germany, India, Israel, Japan, New Zealand, Spain, United Kingdom, United States
Contacts
Public ContactClinical Trial Mailbox
Gilead Sciences International Ltd.
Outcome results
None listed